The objective of this research is to develop efficient and rapid procedures for synthesizing polynucleotides and polynucleotide derivatives possessing any desired sequence of nucleotide units. The approach is to extend and combine current methodology developed in this laboratory, for stepwise and block syntheses utilizing phosphite-triester intermediates, to the construction of a variety of polymers capable of binding selectively to single stranded DNA. These polymers will be examined as primers for enzymatic chain extension and ligation, with phi X174 single strand DNA as a template. Attention will be given not only to synthesis of substances possessing phosphodiester links and base sequences fully complementary to a region on the template strand, but also to synthesis of novel primers with uncharged backbones (e.g. phosphotriester links); backbones with varying charge distributions, and sequences containing one or more bases not complementary to the template. New reactions observed in this laboratory for selectively removing N-protecting groups on the cytosine, adenine, and guanine rings and for generating oligonucleotide derivatives from unprotected nucleosides will be employed in the synthesis of these primers.